One objective of this study is to determine whether the fatty liver resulting from administration of tetracycline is due to an impairment of the mechanisms of hepatic secretion of triglyceride into the very low density lipoprotein (VLDL) of serum; an additional objective is to determine whether the severity and duration of fatty liver (judged by morphological and chemical estimates of triglyceride accumulation) can be correlated with functional impairment of hepatic function (judged by various biochemical indices). A critical aspect of the proposed research is the evaluation of the increased hepatotoxicity to tetracycline demonstrated by pregnant and nonpregnant females, in contrast to the male animal. It is conceivable that this apparent difference in sensitivity to tetracycline reflects modification of rates of hepatic secretion of triglyceride by progestational, estrogenic, or androgenic drugs or steroids. We propose, therefore, to investigate the biosynthesis and secretion of lipids and lipoproteins by isolated perfused livers from female, male, and pregnant animals, and from rats treated with tetracycline; we will examine the effects on hepatic formation of VLDL when tetracycline or related drugs are added to the perfusate in vitro. Finally, and perhaps of greatest significance, the influence of various sex related steroids on hepatic morphology, on metabolism of triglycerides, and on other biochemical criteria of function will be evaluated.